Fibrates in the treatment of cardiovascular risk and atherogenic dyslipidaemia

Abstract

New data have emerged over the last few years about the role of fibrates in treatment of microvascular and macrovascular disease. Endpoint studies have been conducted with fibrates in coronary heart disease (CHD) since 1971 and initial results were contradictory. Fibrates later showed benefits in patients with low HDL-C and low LDL-C. The prominence ascribed to the lipid triad of the metabolic syndrome and the increasing prevalence of diabetes has increased the topicality of fibrates given their main action of converting small dense to light buoyant LDL. The Fenofibrate Intervention in Endpoint Lowering in Diabetes (FIELD) study has carried on the tradition. Fenofibrate therapy in 9795 patients comprising a mixed low-risk primary and a medium-risk secondary prevention cohort resulted in an 11% reduction in coronary events (P = 0.16), a similar but significant reduction in cardiovascular events (P = 0.04; number-needed-to-treat = 70). The benefits were concentrated in primary prevention and on nonfatal myocardial events, and post-hoc greater effects were seen in patients with moderate hypertriglyceridaemia (>2.3 mmol/l) and low HDL-C, as had previously been noted in a trial with bezafibrate. Safety was generally good, including in combination with statins, but old concerns about sudden death, pancreatitis and venous thrombosis returned. Unexpected benefits were seen with fenofibrate for microvascular endpoints including microalbuminuria and retinopathy. Fenofibrate and bezafibrate are reasonable second-line therapies for dyslipidaemia and in diabetes, and well tolerated in combination therapy. The benefits of fenofibrate for microvascular disease and its potential role in combination therapy require further confirmation.